In the context of NETosis (neutrophil extracellular trap formation), which enzymatic step is essential for chromatin decondensation and NET extrusion, and which pathological condition is it most directly implicated in?

• A MPO (myeloperoxidase) generating hypochlorous acid — implicated primarily in bacterial killing within neutrophil phagolysosomes
• B Caspase-1 cleaving gasdermin D — implicated in macrophage pyroptosis, not NETosis
• C Elastase translocating to the nucleus to degrade NF-κB — implicated in apoptosis-dependent NET release
• D PAD4 (peptidylarginine deiminase 4) citrullinating histones — implicated in venous thromboembolism and autoimmune tissue damage ✓

Explanation

PAD4 (peptidylarginine deiminase 4) citrullinates arginine residues on histones H3 and H4, causing chromatin decondensation — a prerequisite for suicidal NETosis. NET extrusion involves nuclear membrane rupture, chromatin-MPO-elastase complex release into cytoplasm, and eventual plasma membrane rupture. NETs contribute to thrombosis (platelet and fibrin trapping), SLE (anti-NET antibodies and DNA immunogenicity), vasculitis, and ischemia-reperfusion injury. PAD4 inhibitors are in clinical trials for autoimmune and thrombotic conditions.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.